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Digoxin is commonly prescribed for heart failure and atrial fibrillation, but there is limited data on its safety in patients with chronic kidney disease (CKD). We conducted a population-based cohort study using the pre-end stage renal disease (ESRD) care program registry and the National Health Insurance Research Database in Taiwan. Of advanced CKD patient cohort (N = 31,933), we identified the digoxin user group (N = 400) matched with age and sex non-user group (N = 2,220). Multivariable Cox proportional hazards and sub-distribution hazards models were used to evaluate the association between digoxin use and the risk of death, cardiovascular events (acute coronary syndrome, ischemic stroke, or hemorrhagic stroke) and renal outcomes (ESRD, rapid decline in estimated glomerular filtration rate-eGFR, or acute kidney injury). Results showed that all-cause mortality was higher in the digoxin user group than in the non-user group, after adjusting for covariates (adjusted hazard ratio, aHR 1.63; 95% CI 1.23-2.17). The risk for acute coronary syndrome (sub-distribution hazard ratio, sHR 1.18; 95% CI 0.75-1.86), ischemic stroke (sHR 1.42; 95% CI 0.85-2.37), and rapid eGFR decline (sHR 1.00 95% CI 0.78-1.27) was not significantly different between two groups. In conclusion, our study demonstrated that digoxin use was associated with increased mortality, but not cardiovascular events or renal function decline in advanced CKD patients. This finding warns the safety of prescribing digoxin in this population. Future prospective studies are needed to overcome the limitations of cohort study design.

There is no clear evidence how effective the antiresorptive (AR) drugs alendronate and raloxifene are at reducing risk of second hip fracture and mortality in dialysis populations. The purpose of this study was to compare the risk of hospitalization for second hip fracture and risk of mortality between AR user and non-user groups in Taiwanese women on long-term dialysis with hip fractures. We conducted a retrospective cohort study using Taiwan National Health Insurance Research Datasets. Long-term dialysis women older than 50 years with newly diagnosed hip fractures and new to AR therapy from 2005 to 2011 were recruited. The patients were divided into AR users and non-users and matched by propensity score. We used Cox Proportional Hazards models to assess association of AR with risks of second hip fracture and mortality. Totally, 1,079 dialysis patients were included, and after matching, we were left with 74 AR users and 74 non-users. AR users did not show a significant reduction in the incidence of second hip fracture compared with non-users (adjusted Hazard Ratio (HR): 0.91, 95% CI: 0.30-2.76), and alendronate users exhibited higher risk of second hip fracture compared with raloxifene users (adjusted HR: 2.80, 95% CI: 0.42-18.79). In addition, AR users were found to have significantly lower 1- and 2-year mortality rates than the non-users (1- year: adjusted HR 0.25, 95% CI, 0.07-0.90; 2-year: 0.35, 95%CI: 0.17-0.72). AR treatment did not significantly improve the risk of second hip fracture but significantly reduce mortality in older women on dialysis. Further clinical trials on effectiveness of AR medications for dialysis populations should be warranted.

BackgroundThe accurate assessment of liver fibrosis among hemodialysis patients with chronic hepatitis C (CHC) is important for both treatment and for follow up strategies. Applying the non-invasive methods in general population with viral hepatitis have been successful but the applicability of the aminotransferase/platelet ratio index (APRI) or the fibrosis-4 index (FIB-4) in hemodialysis patients need further evaluation.Materials and methodsWe conducted a prospective, multi-center, uremic cohort to verify the applicability of APRI and FIB-4 in identifying liver fibrosis by reference with the standard transient elastography (TE) measures.ResultsThere were 116 CHC cases with valid TE were enrolled in our analysis. 46 cases (39.6%) were classified as F1, 35 cases (30.2%) as F2, 11 cases (9.5%) as F3, and 24 cases (20.7%) as F4, respectively. The traditional APRI and FIB-4 criteria did not correctly identify liver fibrosis. The optimal cut-off value of APRI was 0.28 and of FIB-4 was 1.91 to best excluding liver cirrhosis with AUC of 76% and 77%, respectively. The subgroup analysis showed that female CHC hemodialysis patients had better diagnostic accuracy with 74.1% by APRI. And CHC hemodialysis patients without hypertension had better diagnostic accuracy with 78.6% by FIB-4.ConclusionsThis study confirmed the traditional category level of APRI and FIB-4 were unable to identify liver fibrosis of CHC hemodialysis patients. With the adjusted cut-off value, APRI and FIB-4 still showed suboptimal diagnostic accuracy. Our results suggest the necessary of TE measures for liver fibrosis in the CHC uremic population.

BackgroundDepression is common in dialysis patients, but the clinical impact of this condition is poorly defined.MethodsOut of 57,703 patients starting dialysis during 2000-2007 recorded in the National Health Insurance Research Database of Taiwan, we identified 2,475 patients with a clinical diagnosis of depression, and compared them with 1:5 age- and sex-matched patients without a depression diagnosis (n = 12,375). Patients were followed up for hospitalisation due to severe infections, major adverse cardiovascular events (MACE) and death. Multivariable Cox regression and competing risk analyses (accounting for death when appropriate) were used to estimate risk associations.ResultsPatients with depression had a higher frequency of comorbidities. During a mean follow-up of 3.2 years, 1,140 severe infections, 806 MACE, and 1,121 deaths were recorded. Compared to controls, patients with depression were at increased risk of death (adjusted hazard ratio 1.24; 95%CI 1.16-1.33). Patients with depression were also at higher risk of severe (1.14; 1.06-1.22) and fatal infections (death within 30 days, 1.22; 1.09-1.35), attributed mainly to sepsis (1.19; 1.08-1.31), septic shock (1.36; 1.13-1.62) and pneumonia (1.19; 1.07-1.33). Conversely, no association was observed between depression and the MACE risk (1.04; 0.94-1.15).ConclusionDialysis patients with depression are associated with increased risk of infections and death.

A common complication of chronic kidney disease (CKD), anemia can influence glycated hemoglobin (HbA1c) levels. In diabetic patients, anemia occurs earlier and with higher severity over the course of CKD stages. To elucidate the effect of hemoglobin (Hb) on the predictive value of HbA1c, we enrolled 1558 diabetic patients with stages 3-4 CKD, categorized according to baseline Hb and HbA1c quartiles. Linear regression revealed that higher HbA1c correlated significantly with higher Hb in the Hb < 10 g/dL group (β = 0.146, P = 0.004). A fully-adjusted Cox regression model revealed worse clinical outcomes in patients with higher HbA1c quartiles in the Hb ≥ 10 g/dL group. Hazard ratios for end-stage renal disease (ESRD), all-cause mortality, and composite endpoint (cardiovascular events and all-cause mortality) in patients with Hb ≥ 10 g/dL and the highest HbA1c quartile were 1.92 (95% confidence interval [CI], 1.17-3.15), 1.76 (95% CI, 1.02-3.03), and 1.54 (95% CI, 1.03-2.31), respectively. By contrast, HbA1c was not associated with clinical outcomes in the Hb < 10 g/dL group. In conclusion, in stages 3-4 diabetic CKD, higher HbA1c is associated with a higher risk of poor clinical outcomes in patients with Hb ≥ 10 g/dL.

Inadequate care of chronic kidney disease (CKD) is common and may be associated with adverse outcomes after dialysis. The nationwide pre-end-stage renal disease pay for performance program (P4P) has been implemented in Taiwan to improve quality of CKD care. However, the effectiveness of the P4P program in improving the outcomes of pre-dialysis care and dialysis is uncertain. We conducted a longitudinal cohort study. Patients who newly underwent long-term dialysis (≥3 mo) between 2007 and 2009 were identified from the Taiwan National Health Insurance Research Database. Based on the patient enrolment of the P4P program, they were categorized into P4P or non-P4P groups. We analysed pre-dialysis care, healthcare expenditures, and mortality between two groups. Among the 26 588 patients, 25.5% participated in the P4P program. The P4P group received significantly better quality of care, including a higher frequency of glomerular filtration rate measurement and CKD complications survey, a higher rate of vascular access preparation, and more frequent use of arteriovenous fistulas than the non-P4P group did. The P4P group had a 68.4% reduction of the 4-year total healthcare expenditure (excluding dialysis fee), which is equivalent to US$345.7 million, and a significant 22% reduction in three-year mortality after dialysis (hazard ratio 0.78, 95% confidence interval: 0.75-0.82, P < 0.001) compared with the non-P4P group. P4P program improves quality of pre-dialysis CKD care, and provide survival benefit and a long-term cost saving for dialysis patients.

BACKGROUND:Fluid overload is not only the characteristic but also an important complication in chronic kidney disease (CKD) patients. Angiopoietin-2 (Angpt2) disturbs endothelium and vessel permeability, which may induce fluid overload. The aim of this study is to examine the interaction between fluid status and Angpt2 in adverse renal outcomes of CKD. METHODS:This cohort study enrolled 290 patients with CKD stages 3-5 from January 2011 to December 2011 and followed up until December 2015. Fluid status was presented as overhydration (OH) value measured by body composition monitor, while OH>1.1L was defined as fluid overload. Renal outcomes were defined as commencing dialysis and rapid renal function decline (the slope of estimated glomerular filtration rate < -5 ml/min/1.73 m2/y). RESULTS:During a mean follow-up of 38.6±18.3 months, 125 (43.1%) patients progressed to commencing dialysis and 99(34.7%) patients presented rapid renal function decline. All patients were stratified by OH of 1.1L and the median of circulating Angpt2. These patients with both OH>1.1L and high circulating Angpt2 were more likely to reach commencing dialysis compared to other groups. The risks for commencing dialysis and rapid renal function decline were significantly higher in patients with OH>1.1L and high circulating Angpt2 level compared to those with OH≦1.1L and low circulating Angpt2 (2.14, 1.21-3.78, P = 0.009; 4.96, 1.45-16.97, P = 0.01). There was a significant interaction between OH level and circulating Angpt2 in entering dialysis (P-interaction = 0.02). CONCLUSIONS:Fluid overload and Angpt2 might have a synergistic effect on adverse renal outcomes in CKD patients.

Patients with chronic kidney disease (CKD) are more readily prone to have impaired physical activity than the general population. The aim of this study is to examine the relationship between physical activity and adverse clinical outcomes and quality of life (QOL) in CKD. One hundred and sixty-one patients with CKD stages 1-5 was enrolled from February 2013 to September 2013 and followed up until June 2016. Physical activity was measured using high handgrip strength, 30-second chair stand, and 2-minute step. The QOL was assessed using the Taiwan version of the World Health Organization Quality of Life-BREF. Clinical outcomes included commencing dialysis, major adverse cardiovascular events (MACEs), and first hospitalization. Of all participants, 1 kgf increase in handgrip strength was significantly associated with 0.13 score increase in total scores of QOL and 0.05 score increase in physical domain of QOL in adjusted analysis. One time increase in 30-second chair stand was significantly correlated with 0.14 score increase in psychological domain of QOL. Over a mean follow-up period of 29.1±11.2 months, 37 (23.0%) reached commencing dialysis, 11(6.8%) had MACEs, and 50(31.1%) had first hospitalization. High handgrip strength (hazard ratio (HR): 0.89, 95% CI: 0.84-0.96) and high 2-minute step (HR: 0.04, 95% CI: 0.01-0.95) were significantly associated with decreased risk for commencing dialysis in multivariate analysis. Thirty-second chair-stand was negatively associated with MACEs (HR: 0.65, 95%CI: 0.47-0.89) and first hospitalization (HR: 0.84, 95%CI: 0.74-0.95). In conclusion, physical activity is a potential predictor of QOL and adverse clinical outcomes in patients with CKD.

Impairment of physical function and abnormal body composition are the major presentations in patients with chronic kidney disease (CKD). The aim of this study is to investigate the relationship between body composition and physical function in CKD patients.This cross-sectional study enrolled 172 of CKD stages 1-5 from February 2013 to September 2013. Handgrip strength (upper extremity muscle endurance), 30-second chair-stand test (lower extremity muscle endurance) and 2-minute step test (cardiorespiratory endurance) were used as indices of physical function. Body composition, including fluid status (extracellular water/total body water, ECW/TBW), lean tissue index (LTI), and fat tissue index (FTI), was measured using a bioimpedance spectroscopy method.All patients with high ECW/TBW had lower handgrip strength and 30-second chair-stand than those with low ECW/TBW (P

Increased incidence of erectile dysfunction (ED) has been reported among patients with sleep apnea (SA). However, this association has not been confirmed in a large-scale study. We therefore performed a population-based cohort study using Taiwan National Health Insurance (NHI) database to investigate the association of SA and ED. From the database of one million representative subjects randomly sampled from individuals enrolled in the NHI system in 2010, we identified adult patients having SA and excluded those having a diagnosis of ED prior to SA. From these suspected SA patients, those having SA diagnosis after polysomnography were defined as probable SA patients. The dates of their first SA diagnosis were defined as their index dates. Each SA patient was matched to 30 randomly-selected, age-matched control subjects without any SA diagnosis. The control subjects were assigned index dates as their corresponding SA patients, and were ensured having no ED diagnosis prior to their index dates. Totally, 4,835 male patients with suspected SA (including 1,946 probable SA patients) were matched to 145,050 control subjects (including 58,380 subjects matched to probable SA patients). The incidence rate of ED was significantly higher in probable SA patients as compared with the corresponding control subjects (5.7 vs. 2.3 per 1000 patient-year; adjusted incidence rate ratio = 2.0 [95% CI: 1.8-2.2], p

A higher body mass index (BMI) appears to be reversely associated with mortality in dialysis patients. Moreover, although women have better survival in chronic kidney disease (CKD), this survival advantage is cancelled in dialysis. The association between BMI and mortality and the gender difference remain controversial in advanced CKD.This study enrolled 3,320 patients (1,938 men and 1,382 women) from southern Taiwan who had CKD stages 3-5 with a BMI of 15.0-35.0 kg/m2.During a median 2.9-year follow-up, there were 328 (16.9%) all-cause mortality and 319 (16.5%) cardiovascular (CV) events and death in male patients, 213 (15.4%) all-cause mortality and 224 (16.2%) CV events and death in female patients. Compared with the reference BMI of 27.6-30.0 kg/m2 in an adjusted Cox model, lower-BMI groups in men, BMI 15.0-20.0 kg/m2 and 20.1-22.5 kg/m2, were associated with higher risks of all-cause mortality: hazard ratios (HRs) 3.19 (95% confidence interval [CI], 1.97-5.18) and 2.01 (95% CI, 1.29-3.14), respectively. Higher-BMI group in men, BMI 30.1-35.0 kg/m2, was associated with a higher risk of all-cause mortality: HR 1.72 (95% CI, 1.02-2.96). Likewise, lower- and higher-BMI groups in men were associated with a higher risk of CV events and death. In women, these associations between BMI and poor outcomes were not observed.In advanced CKD, there was a reverse J-shaped association between BMI and all-cause mortality, and a U-shaped association between BMI and CV outcomes in men. Neutral associations between BMI and poor outcomes were detected in women. Gender could modify the effect of BMI on mortality in patients with CKD.

Peripheral artery disease (PAD) and low heart rate variability (HRV) are highly prevalent in hemodialysis patients, and both are associated with increased cardiovascular morbidity and mortality. This study aims to examine the suggested relationship between PAD and HRV, and the relationship of parameters before and after hemodialysis. This study enrolled 161 maintenance hemodialysis patients. PAD was defined as ABI < 0.9 in either leg. HRV was performed to assess changes before and after hemodialysis. The change in HRV (△HRV) was defined as post-hemodialysis HRV minus pre-hemodialysis HRV. Patients' clinical parameters were collected from the dialysis records. All HRV parameters except high frequency (HF) % were lower in patients with PAD than patients without PAD, though not achieving significant level. In patients without PAD, HF (P = 0.013), low frequency (LF) % (P = 0.028) and LF/HF (P = 0.034) were significantly elevated after hemodialysis, whereas no significant HRV parameters change was noted in patients with PAD. Serum intact parathyroid hormone was independently associated with △HF (β = -0.970, P = 0.032) and △LF% (β = -12.609, P = 0.049). Uric acid level (β = -0.154, P = 0.027) was negatively associated with △LF/HF in patients without PAD. Our results demonstrated that some of the HRV parameters were significantly increased after hemodialysis in patients without PAD, but not in patients with PAD, reflecting a state of impaired sympatho-vagal equilibrium. Severity of secondary hyperparathyroidism and hyperuricemia contributed to lesser HRV parameters increase after hemodialysis in patients without PAD.

Discontinuation of acute, unplanned dialysis is always an important therapeutic goal in dialysis-requiring patients with existing chronic kidney disease. Only a limited proportion of patients could be weaned off dialysis and remained dialysis-free. Here we performed a multicenter, observational study to investigate factors associated with successful weaning from acute dialysis, and to explore the potential impact of weaning itself on outcomes of patients with chronic kidney disease following urgent-start dialysis. We recruited 440 chronic kidney disease patients with a baseline estimated glomerular filtration rate 1 month died, and 36 (8.6%) were removed from dialysis, with 26 (6.2%) remaining alive and dialysis-free. Logistic regression analysis found that age ≧ 65 years, ischemic acute tubular necrosis, nephrotoxic exposure, urinary obstruction, and higher predialysis estimated glomerular filtration rate and serum hemoglobin were predictors of weaning off dialysis. After adjustment for propensity scores for dialysis weaning, Cox proportional hazards models showed successful weaning from dialysis (adjusted hazard ratio 0.06; 95% confidence interval 0.01 to 0.35), along with a history of hypertension and serum albumin, were independent protectors for early death. Conversely, a history of stroke, peripheral arterial disease and cancer predicted the occurrence of early mortality. In conclusion, this prospective cohort study shows that compared to patients with chronic kidney disease who became end-stage renal disease after acute dialysis, patients who could be weaned off acute dialytic therapy were associated with reduced risk of premature death over a 2-year observation period.

Chronic kidney disease (CKD) patients have higher prevalence of major adverse cardiovascular events (MACE) and all-cause mortality. Endothelial damage and dysfunction have been regarded as early portents of MACE in CKD patients. Angiopoietin-2 (Ang-2) impairs endothelial function and promotes aberrant neovascularization. The aim of the study was to assess the relationship between circulating Ang-2 and MACE or all-cause mortality in a CKD cohort.A total of 621 pre-dialysis stage 3-5 CKD patients were enrolled from January 2006 to December 2011 and were followed up till October 2014. Plasma Ang-2 was measured in duplicate using commercial enzyme-linked immunosorbent assays (ELISA). Clinical outcomes included MACE or all-cause mortality.Of all patients, 122 (19.8%) reached MACE or all-cause mortality. Seventy-two had MACE, 79 died, and 29 had both MACE and all-cause mortality during the follow-up period of 41.5±28.3 months. Ang-2 quintile was divided at 1405.0, 1730.0, 2160.9, and 2829.9 pg/ml. The adjusted HR of MACE or all-cause mortality for every single higher log Ang-2 was 5.69 (95% CI: 2.00-16.20, P = 0.001). The adjusted HR of MACE or all-cause mortality was 2.48 (95% CI: 1.25-4.90) for patients of quintile 5 compared with those of quintile 1. A longitudinal association between MACE or all-cause mortality and stepwise increases in Ang-2 levels was found (P-trend = 0.008).Ang-2 is an independent predictor of MACE or all-cause mortality in CKD patients. Additional study is necessary in order to explore the mechanism of the association of Ang-2 with adverse outcomes in patients with CKD.

Nonapnea sleep disorders (NASD) and sleep-related problems are associated with poor health outcomes. However, the association between NASD and the development and prognosis of chronic kidney disease (CKD) has not been investigated thoroughly. We explored the association between CKD and NASD in Taiwan.We conducted a population-based study using the Taiwan National Health Insurance database with1,000,000 representative data for the period from January 1, 2000 to December 31, 2009. We investigated the incidence and risk of CKD in 7,006 newly diagnosed NASD cases compared with 21,018 people without NASD matched according to age, sex, index year, urbanization, region, and monthly income at a 1:3 ratio.The subsequent risk of CKD was 1.48-foldhigher in the NASD cohort than in the control cohort (95% confidence interval [CI] = 1.26-1.73, p< 0.001). Men, older age, type 2 diabetes mellitus, and gout were significant factors associated with the increased risk of CKD (p< 0.001). Among different types of NASDs, patients with insomnia had a 52% increased risk of developing CKD (95%CI = 1.23-1.84; P

BACKGROUND:To increase the survival span after dialysis in patients with end-stage renal disease (ESRD), identifying specific cancer risks is crucial in the cancer screening of these patients. The aim of this study was to investigate the risks of various cancers in an incident dialysis group in comparison with a non-dialysis group. METHOD:We conducted a nationwide cohort study by using data from the Taiwan National Health Insurance Research Database. Patients who initially received long-term dialysis between January 1997 and December 2004, were selected and defined as the dialysis group and were matched with the non-dialysis patients (control group) according to age, sex, and index year. Competing risk analysis was used to estimate cumulative incidence and subdistribution hazard ratios (SHRs) of the first cancer occurrence. RESULTS:After consideration for the competing risk of mortality, the dialysis group showed a significantly higher 7-year cancer incidence rate than did the control group (6.4%; 95% confidence interval [CI], 6.0%-6.7% vs 1.7%; 95% CI, 1.4%-2.1%; P

BACKGROUND: Chronic kidney disease (CKD) and hepatitis C virus (HCV) infection are closely linked and both increase patient mortality. The association of HCV and risk of developing end-stage renal disease (ESRD) has not been analyzed with competing risk model. METHOD: We enrolled a prospective cohort of 4,185 patients (mean age, 62 years; 41% female) registered in the CKD integrated care program at two affiliated hospitals of Kaohsiung Medical University in Taiwan between November 11, 2002 and May 31, 2009. With competing risk model, we analyzed the association of HCV infection, defined by seropositive of anti-HCV antibody, and hepatitis B virus (HBV) infection, defined by seropositive of HBV surface antigen, with the risk of entering ESRD. RESULTS: The prevalence of HCV infection was 7.6% and it increased with the CKD stages (trend test, P

The pathophysiological mechanisms of renal function progression in chronic kidney disease (CKD) have still not been completely explored. In addition to well-known traditional risk factors, non-traditional risk factors, such as endothelial dysfunction, have gradually attracted physicians' attention. Angiopoietin-2 (Ang-2) impairs endothelial function through preventing angiopoietin-1 from binding to Tie2 receptor. Whether Ang-2 is associated with renal function progression in CKD is unknown.This study enrolled 621 patients with stages 3-5 CKD to assess the association of circulating Ang-2 with commencing dialysis, doubling creatinine and rapid decline in renal function (the slope of estimated glomerular filtration rate (eGFR) greater than 5 ml/min per 1.73 m2/y) over follow-up of more than 3 years.Of all patients, 224 patients (36.1%) progressed to commencing dialysis and 165 (26.6%) reached doubling creatinine. 85 subjects (13.9%) had rapid decline in renal function. Ang-2 quartile was divided at 1494.1, 1948.8, and 2593.1 pg/ml. The adjusted HR of composite outcomes, either commencing dialysis or doubling creatinine was 1.53 (95% CI: 1.06-2.23) for subjects of quartile 4 compared with those of quartile 1. The adjusted OR for rapid decline in renal function was 2.96 (95% CI: 1.13-7.76) for subjects of quartile 4 compared with those of quartile 1. The linear mixed-effects model shows a more rapid decrease in eGFR over time in patients with quartile 3 or more of Ang-2 than those with the lowest quartile of Ang-2.Ang-2 is an independent predictor of adverse renal outcome in CKD. Further study is needed to identify the pathogenic role of Ang-2 in CKD progression.

P wave parameters measured by 12-lead electrocardiogram (ECG) are commonly used as a noninvasive tool to evaluate left atrial enlargement. This study was designed to assess whether P wave parameters were associated with renal outcomes in chronic kidney disease (CKD) patients. This longitudinal study enrolled 439 patients with CKD stages 3-5. Renal end points were defined as the commencement of dialysis or death. Change in renal function was measured using the estimated glomerular filtration rate (eGFR) slope. We measured two ECG P wave parameters corrected for heart rate, i.e., corrected P wave dispersion and corrected maximum P wave duration. The values of P wave dispersion and maximum P wave duration were 88.8±21.7 ms and 153.3±21.7 ms, respectively. During the follow-up period (mean, 25.2 months), 95 patients (21.6%) started hemodialysis and 30 deaths (6.8%) were recorded. Multivariate Cox regression analysis identified that increased P wave dispersion [hazard ratio (HR), 1.020; 95% confidence interval (CI), 1.009-1.032; P

BACKGROUND AND AIM: Metabolic syndrome (MetS), albuminuria, and the Framingham Risk Score (FRS) are significant predictors for cardiovascular disease (CVD). However, the relationship and clinical significance of these CVD predictors in individuals with a family history of end-stage renal disease (ESRD) are unclear. We investigated the association of relatives of hemodialysis (HD) patients with MetS, albuminuria, and the FRS. METHODS: One hundred and sixty-six relatives of HD patients and 374 age- and sex- matched community controls were enrolled. MetS was defined using the Adult Treatment Panel III for Asians. Albuminuria was defined as urine albumin-to-creatinine ratio ≥ 30 mg/g. CVD risk was evaluated by the FRS. RESULTS: A significantly higher prevalence of MetS (19.9% vs. 12.5%, P = 0.026), albuminuria (12.7% vs. 5.1%, P = 0.002) and high FRS risk ≥ 10% of 10-year risk (15.7% vs. 8.5%, P = 0.013) was found in relatives of HD patients compared to their counterpart controls. In multivariate analysis, being relatives of HD patients (vs. controls) was an independent determinant for MetS (odds ratio [OR], 1.785; 95% confidence interval [CI], 1.045 to 3.050), albuminuria (OR, 2.891; 95% CI, 1.431 to 5.841), and high FRS risk (OR, 1.863; 95% CI, 1.015 to 3.418). Higher low-density lipoprotein cholesterol (OR, 1.034; 95% CI, 1.017 to 1.052) and betel nut chewing (OR, 13.994; 95% CI, 3.384 to 57.871) were independent determinants for having a high FRS risk in relatives of HD patients. CONCLUSIONS: Being relatives of HD patients was independently associated with MetS, albuminuria and high FRS risk, suggesting family members of ESRD patients may have higher CVD risks through the interactions of renal risk factors. Proactive surveillance of these CVD predictors and preventive strategies should be targeted to this high-risk population.

Fluid overload is one of the characteristics in chronic kidney disease (CKD). Changes in extracellular fluid volume are associated with progression of diabetic nephropathy. Not only diabetes but also fluid overload is associated with cardiovascular risk factors The aim of the study was to assess the interaction between fluid overload, diabetes, and cardiovascular risk factors, including arterial stiffness and left ventricular function in 480 patients with stages 4-5 CKD. Fluid status was determined by bioimpedance spectroscopy method, Body Composition Monitor. Brachial-ankle pulse wave velocity (baPWV), as a good parameter of arterial stiffness, and brachial pre-ejection period (bPEP)/brachial ejection time (bET), correlated with impaired left ventricular function were measured by ankle-brachial index (ABI)-form device. Of all patients, 207 (43.9%) were diabetic and 240 (50%) had fluid overload. For non-diabetic CKD, fluid overload was associated with being female (β = -2.87, P = 0.003), heart disease (β = 2.69, P = 0.04), high baPWV (β = 0.27, P = 0.04), low hemoglobin (β = -1.10, P < 0.001), and low serum albumin (β = -5.21, P < 0.001) in multivariate analysis. For diabetic CKD, fluid overload was associated with diuretics use (β = 3.69, P = 0.003), high mean arterial pressure (β = 0.14, P = 0.01), low bPEP/ET (β = -0.19, P = 0.03), low hemoglobin (β = -1.55, P = 0.001), and low serum albumin (β = -9.46, P < 0.001). In conclusion, baPWV is associated with fluid overload in non-diabetic CKD and bPEP/bET is associated with fluid overload in diabetic CKD. Early and accurate assessment of these associated cardiovascular risk factors may improve the effects of entire care in late CKD.

Estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) study or the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations may not be accurate for Asians; thus, we developed modified eGFR equations for Taiwanese adults.This cross-sectional study compared the Taiwanese eGFR equations, the MDRD study, and the CKD-EPI equations with inulin clearance (Cin). A total of 695 adults including 259 healthy volunteers and 436 CKD patients were recruited. Participants from the Kaohsiung Medical University Hospital were used as the development set (N = 556) to develop the Taiwanese eGFR equations, whereas participants from the National Taiwan University Hospital were used as the validation set (N = 139) for external validation.The Taiwanese eGFR equations were developed by using the extended Bland-Altman plot in the development set. The Taiwanese MDRD equation was 1.309 × MDRD0.912, Taiwanese CKD-EPI was 1.262×CKD-EPI0.914 and Taiwanese four-level CKD-EPI was 1.205 × four-level CKD-EPI0.914. In the validation set, the Taiwanese equations had the lowest bias, the Taiwanese equations and the Japanese CKD-EPI equation had the lowest RMSE, whereas the Taiwanese and the Japanese equations had the best precision and the highest P30 among all equations. However, the Taiwanese MDRD equation had higher concordance correlation than did the Taiwanese CKD-EPI, the Taiwanese four-level CKD-EPI and the Japanese equations. Moreover, only the Taiwanese equations had no proportional bias among all of the equations. Finally, the Taiwanese MDRD equation had the best diagnostic performance in terms of ordinal logistic regression among all of the equations.The Taiwanese MDRD equation is better than the MDRD, CKD-EPI, Japanese, Asian, Thai, Taiwanese CKD-EPI, and Taiwanese four-level CKD-EPI equations for Taiwanese adults.

Dyslipidemia is highly prevalent in patients with chronic kidney disease (CKD) and the relationship between dyslipidemia with renal outcomes in patients with moderate to advanced CKD remains controversial. Hence, our objective is to determine whether dyslipidemia is independently associated with rapid renal progression and progression to renal replacement therapy (RRT) in CKD patients. The study analyzed the association between lipid profile, RRT, and rapid renal progression (estimated glomerular filtration rate [eGFR] slope

The Framingham Risk Score (FRS) was developed to predict coronary heart disease in various populations, and it tended to under-estimate the risk in chronic kidney disease (CKD) patients. Our objectives were to determine whether FRS was associated with cardiovascular events, and to evaluate the role of new risk markers and echocardiographic parameters when they were added to a FRS model. This study enrolled 439 CKD patients. The FRS is used to identify individuals categorically as "low" (4.7 cm, left ventricular hypertrophy or left ventricular ejection fraction

BACKGROUND: The comorbidity index is a predictor of mortality in dialysis patients but there are few reports for predicting elderly dialysis mortality and national population-based cost studies on elderly dialysis. The aim of this study was to evaluate the long-term mortality of incident elderly dialysis patients using the Deyo-Charlson comorbidity index (CCI) and to assess the inpatient and outpatient visits along with non-dialysis costs. METHODS: Data were obtained from catastrophic illness registration of the Taiwan National Health Insurance Research Database. Incident elderly dialysis patients (age ≥75 years) receiving hemodialysis for more than 90 days between Jan 1, 1998, and Dec 31, 2007, were included. Baseline comorbidities were determined one year prior to the first dialysis day according to ICD-9 CM codes. Survival time, mortality rate, hospitalization time, outpatient visit frequency, and costs were calculated for different age and CCI groups. RESULTS: In 10,759 incident elderly hemodialysis patients, hazard ratios for all-cause mortality were significantly increased in the different age groups (p < 0.001) and CCI patients (p < 0.001). Death rates increased with both increasing age and CCI score. High comorbidity incident hemodialysis and elderly patients were found to have increased length of hospital stay and total hospitalization costs. CONCLUSIONS: This population-based cohort study indicated that both age and higher CCI values were predictors of survival in incident elderly hemodialysis. Increased costs and mortality rates were evident in the oldest patients and in those with high CCI scores. Conservative treatment might be considered in high comorbidity and low-survival rate end stage renal disease (ESRD) patients.

BACKGROUND: In the chronic kidney disease (CKD) population, the impact of serum potassium (sK) on renal outcomes has been controversial. Moreover, the reasons for the potential prognostic value of hypokalemia have not been elucidated. DESIGN PARTICIPANTS & MEASUREMENTS: 2500 participants with CKD stage 1-4 in the Integrated CKD care program Kaohsiung for delaying Dialysis (ICKD) prospective observational study were analyzed and followed up for 2.7 years. Generalized additive model was fitted to determine the cutpoints and the U-shape association between sK and end-stage renal disease (ESRD). sK was classified into five groups with the cutpoints of 3.5, 4, 4.5 and 5 mEq/L. Cox proportional hazard regression models predicting the outcomes were used. RESULTS: The mean age was 62.4 years, mean sK level was 4.2±0.5 mEq/L and average eGFR was 40.6 ml/min per 1.73 m(2). Female vs male, diuretic use vs. non-use, hypertension, higher eGFR, bicarbonate, CRP and hemoglobin levels significantly correlated with hypokalemia. In patients with lower sK, nephrotic range proteinuria, and hypoalbuminemia were more prevalent but the use of RAS (renin-angiotensin system) inhibitors was less frequent. Hypokalemia was significantly associated with ESRD with hazard ratios (HRs) of 1.82 (95% CI, 1.03-3.22) in sK 5 mEq/L conferred 1.6-fold (95% CI,1.09-2.34) increased risk of ESRD compared with sK = 4.5-5 mEq/L. Hypokalemia was also associated with rapid decline of renal function defined as eGFR slope below 20% of the distribution range. CONCLUSION: In conclusion, both hypokalemia and hyperkalemia are associated with increased risk of ESRD in CKD population. Hypokalemia is related to increased use of diuretics, decreased use of RAS blockade and malnutrition, all of which may impose additive deleterious effects on renal outcomes.

BACKGROUND: Comorbid conditions are highly prevalent among patients with end-stage renal disease (ESRD) and index score is a predictor of mortality in dialysis patients. The aim of this study is to perform a population-based cohort study to investigate the survival rate by age and Charlson comorbidity index (CCI) in incident dialysis patients. METHODS: Using the catastrophic illness registration of the Taiwan National Health Insurance Research Database for all patients from 1 January 1998 to 31 December 2008, individuals newly diagnosed with ESRD and receiving dialysis for more than 90 days were eligible for our study. Individuals younger than 18 years or renal transplantation patients either before or after dialysis were excluded. We calculated the CCI, age-weighted CCI by Deyo-Charlson method according to ICD-9 code and categorized CCI into six groups as index scores 15. Cox regression models were used to analyze the association between age, CCI and survival, and the risk markers of survival. RESULTS: There were 79,645 incident dialysis patients, whose mean age (± SD) was 60.96 (±13.92) years; 51.43% of patients were women and 51.2% were diabetic. In cox proportional hazard models and stratifying by age, older patients had significantly higher mortality than younger patients. The mortality risk was higher in persons with higher CCI as compared with low CCI. Mortality increased steadily with higher age or comorbidity both for unadjusted and for adjusted models. For all age groups, mortality rates increased in different CCI groups with the highest rates occurring in the oldest age groups. CONCLUSIONS: Age and CCI are both strong predictors of survival in Taiwan. The older age or higher comorbidity index in incident dialysis patient is associated with lower long-term survival rates. These population-based estimates may assist clinicians who make decisions when patients need long-term dialysis.

Fluid overload is one of the major presentations in patients with late stage chronic kidney disease (CKD). Diabetes is the leading cause of renal failure, and progression of diabetic nephropathy has been associated with changes in extracellular fluid volume. The aim of the study was to assess the association of fluid overload and diabetes in commencing dialysis and rapid renal function decline (the slope of estimated glomerular filtration rate (eGFR) less than -3 ml/min per 1.73 m(2)/y) in 472 patients with stages 4-5 CKD. Fluid status was determined by bioimpedance spectroscopy method, Body Composition Monitor. The study population was further classified into four groups according to the median of relative hydration status (△HS =fluid overload/extracellular water) and the presence or absence of diabetes. The median level of relative hydration status was 7%. Among all patients, 207(43.9 %) were diabetic. 71 (15.0%) subjects had commencing dialysis, and 187 (39.6%) subjects presented rapid renal function decline during a median 17.3-month follow-up. Patients with fluid overload had a significantly increased risk for commencing dialysis and renal function decline independent of the presence or absence of diabetes. No significantly increased risk for renal progression was found between diabetes and non-diabetes in late CKD without fluid overload. In conclusion, fluid overload has a higher predictive value of an elevated risk for renal progression than diabetes in late CKD.

BACKGROUND: Cardiovascular disease (CVD) is a leading cause of mortality and morbidity in patients with chronic kidney disease (CKD). In Taiwan, CVD is dominated by strokes but there is no robust evidence for a causal relationship between CKD and stroke. This study aimed to explore such causal association. METHODS: We conducted a nationwide retrospective cohort study based on the Taiwan National Health Insurance Research Database from 2004 to 2007. Each patient identified was individually tracked for a full three years from the index admission to identify those in whom any type of stroke developed. The study cohort consisted of patients hospitalized with a principal diagnosis of CKD and no traditional cardiovascular risk factors at baseline (n = 1393) and an age-matched control cohort of patients hospitalized for appendectomies (n = 1393, a surrogate for the general population). Cox proportional hazard regression and propensity score model were used to compare the three-year stroke-free survival rate of the two cohorts after adjustment for possible confounding factors. RESULTS: There were 256 stroke patients, 156 (11.2%) in the study cohort and 100 (7.2%) in the control cohort. After adjusting for covariates, patients with primary CKD had a 1.94-fold greater risk for stroke (95% CI, 1.45-2.60; p

Inflammation is a pathogenic factor in renal injury, but whether inflammation is related to renal outcome in chronic kidney disease (CKD) patients is little known. We thus assess the association of inflammation and renal outcome in an advanced CKD cohort. This study analyzed the association between inflammatory markers, such as C-reactive protein (hsCRP), white blood cell (WBC) count and ferritin, renal replacement therapy (RRT) and rapid renal progression (estimated GFR slope

17α-Hydroxylase/17, 20-lyase deficiency (17OHD) is an autosomal recessive disease causing congenital adrenal hyperplasia and a rare cause of hypertension with hypokalemia. The CYP17A1 gene mutation leads to 17OHD and its clinical features. We described an 18 y/o female with clinical features of 17α-hydroxylase/17, 20-lyase deficiency and characterized the functional consequences of an intronic CYP17A1 mutation. The coding regions and flanking intronic bases of the CYP17A1 gene were amplified by PCR and sequenced. The patient is a compound heterozygote for the previously described p.R358X and IVS1 +2T>C mutations. A first intron splice donor site mutation was re-created in minigene and full-length expression vectors. Pre-mRNA splicing of the variant CYP17A1 intron was studied in transfected cells and in a transformed lymphoblastoid cell line. When the full-length CYP17A1 gene and minigene containing the intronic mutation was expressed in transfected cells, the majority (>90%) of mRNA transcripts were incorrectly spliced. Only the p.R358X transcript was detected in the EBV-transformed lymphoblastoid cell line. The IVS1 +2T>C mutation abolished most 17α-hydroxylase/17, 20-lyase enzyme activity by aberrant mRNA splicing to an intronic pseudo-exon, causing a frame shift and early termination.